Hydroxytyrosol for Colorectal Cancer

Overseen By Kimberly Vu Clinical Research Nurse, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The Methodist Hospital Research Institute

Must be taking: 5FU-based therapy

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Cardiac abnormalities, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Up to 100 weeks

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for advanced or metastatic colorectal cancer. Researchers aim to determine the safety and effectiveness of adding Hydroxytyrosol (HT), a compound found in olives, to standard cancer drugs like FOLFIRI or FOLFOX. Participants will take HT capsules daily alongside their usual cancer treatment until the cancer shows signs of non-response. The trial seeks individuals diagnosed with advanced or metastatic colorectal cancer who can tolerate standard first-line therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients receiving certain treatments like corticosteroids or investigational agents may not be eligible, so it's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that hydroxytyrosol (HT) is generally safe. Studies have demonstrated that taking up to 500 mg per kilogram daily caused no harm, indicating likely safety. This trial uses a much lower dose of just 25 mg per day.

In the U.S., HT is also deemed safe in foods at 5 mg per serving, further supporting its safety profile. However, as this is an early-stage trial, the primary goal is to assess how well people tolerate HT when combined with other cancer treatments.

Overall, current evidence suggests HT is well-tolerated, but ongoing studies aim to confirm this in the context of cancer treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Researchers are excited about Hydroxytyrosol for colorectal cancer because it introduces a potentially powerful antioxidant from olive oil into cancer therapy. Unlike the standard chemotherapy regimens like FOLFIRI and FOLFOX, which primarily target rapidly-dividing cancer cells, Hydroxytyrosol could offer additional benefits by reducing oxidative stress and inflammation, possibly enhancing the overall effectiveness of the treatment. This unique mechanism might help in slowing down disease progression and improving patients' quality of life.

What evidence suggests that Hydroxytyrosol might be an effective treatment for colorectal cancer?

Research has shown that Hydroxytyrosol (HT), which participants in this trial will receive alongside FOLFIRI/FOLFOX and biologics, might help fight colorectal cancer in several ways. It can trigger apoptosis, a process that helps cancer cells die, by boosting certain genes like CASP3. HT also appears to work well with other drugs, such as Cetuximab, to stop cancer cells from multiplying. One study found that HT can reduce the growth of blood vessels that feed tumors by lowering levels of VEGF, a protein involved in this process. Lab studies have also found that HT slows the growth of different colorectal cancer cells. These findings suggest that HT could be a promising addition to cancer treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Abdullah Esmail, MD

Principal Investigator

Houston Methodist Neal Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with advanced or metastatic colorectal cancer. Participants must be suitable for 5FU-based therapy and able to take daily capsules of Hydroxytyrosol (HT). Specific inclusion and exclusion criteria are not provided, but typically involve factors like overall health, prior treatments, and the stage of cancer.

Inclusion Criteria

I am fully active or can carry out light work.

My colorectal cancer is confirmed to be advanced or has spread.

Life expectancy ≥6 months

Exclusion Criteria

I have hepatitis B, C, or HIV that is not under control.

Serum albumin <2.8 g/dL

Total bilirubin >1.5 × ULN or >1.5 mg/dL

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants receive 1 capsule of HT 25 mg daily for 2 weeks before beginning 5FU-based therapy

2 weeks

1 visit (in-person)

Treatment

Participants receive 5FU-based therapy (FOLFIRI/FOLFOX + Biologics) in combination with HT until disease progression or un-tolerated toxicity

Up to 100 weeks

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Hydroxytyrosol

Trial Overview The study tests the safety and effectiveness of adding HT to standard chemotherapy regimens (FOLFIRI/FOLFOX + Biologics) in treating colorectal cancer. Patients will take HT daily before and during their chemo cycles until disease progression or unacceptable side effects occur.

How Is the Trial Designed?

Group I: Hydroxytyrosol (HT) in combination with Folfiri/Folfox Experimental Treatment 1 Intervention

Patients will receive: 1 capsule of HT 25 mg daily for 2 weeks before beginning 5FU-based therapy (FOLFIRI/FOLFOX + Biologics), 1 capsule of HT (25 mg) daily for 2 weeks while receiving the FOLFIRI/FOLFOX + Biologics, until sign of disease progression. The prescribed FOLFIRI/FOLFOX administer as: Irinotecan 180 mg/m² intravenously (IV) over 90 minutes concurrently with Leucovorin 400 mg/m² IV over 120 minutes, followed by Fluorouracil 400-500 mg/m² IV bolus then 2400-3000 mg/m² IV infusion over 4-6 hours with or without, the designated Biologics, a standard dose of Cetuximab or Bevacizumab will be administered in 2-week cycles until disease progression or un-tolerated toxicity

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Published Research Related to This Trial

Hydroxytyrosol (HT) effectively inhibits the growth of prostate cancer cells (LNCaP and C4-2) in a dose-dependent manner while showing no harmful effects on normal prostate cells, indicating its cancer-specific action.

HT induces cell cycle arrest and apoptosis in prostate cancer cells by affecting key signaling pathways, including inhibition of cyclins and activation of apoptotic markers, suggesting its potential as a safe and effective treatment for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells. Zubair, H., Bhardwaj, A., Ahmad, A., et al.[2018]

Hydroxytyrosol, a phenolic compound from olives, is being explored for its potential use as a supplement and preservative in various industries, including nutraceuticals and cosmetics.

The toxicological evaluation of hydroxytyrosol suggests a No Observed Adverse Effects Level (NOAEL) of 500 mg/kg/day, indicating a favorable safety profile for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicological evaluation of pure hydroxytyrosol. Auñon-Calles, D., Canut, L., Visioli, F.[2013]

Hydroxytyrosol, a key antioxidant in virgin olive oil, significantly inhibits the proliferation of cancer cells, specifically human promyelocytic leukaemia (HL60) and colon adenocarcinoma (HT29) cells, at concentrations of approximately 50 and 750 micromol/l, respectively.

The compound induces apoptosis in HL60 cells at concentrations between 50 to 100 micromol/l and causes cell cycle arrest in the G0/G1 phase, suggesting that hydroxytyrosol may play a protective role against cancer by targeting tumor cells while showing no harmful effects on normal human lymphocytes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. Fabiani, R., De Bartolomeo, A., Rosignoli, P., et al.[2019]

In a study involving 28 female Sprague-Dawley rats with induced mammary tumors, hydroxytyrosol significantly inhibited tumor growth and proliferation, showing results comparable to the chemotherapy drug doxorubicin, but with better histopathological outcomes.

Hydroxytyrosol altered the expression of genes related to important cellular processes such as apoptosis and cell cycle regulation, particularly enhancing the expression of Sfrp4, indicating its potential as an anti-cancer agent through multiple biological pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours. Granados-Principal, S., Quiles, JL., Ramirez-Tortosa, C., et al.[2015]

Hydroxytyrosol (HT) demonstrated significant anticancer effects in human leukemia T cells (Jurkat and HL60), with an IC50 of 27.3 µg/mL for Jurkat cells, indicating its potential as a natural treatment for liquid cancers.

HT also exhibited anti-inflammatory properties by reducing nitric oxide levels in murine macrophages (Raw264.7), suggesting it could be beneficial in managing inflammation alongside its anticancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involvement of the PI3K/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity. Parra-Perez, AM., Pérez-Jiménez, A., Gris-Cárdenas, I., et al.[2022]

Nano-capsulated hydroxytyrosol demonstrated significantly greater cytotoxic effects on HT-29 colorectal cancer cells compared to free hydroxytyrosol, with an IC50 of 6 PPM versus 12 PPM after 72 hours, indicating enhanced efficacy of the nano-formulation.

The study found that nano-capsulated hydroxytyrosol effectively induced cell cycle arrest by upregulating the CDKN1A and CDKN1B genes while downregulating the CCND1 gene, suggesting a specific mechanism of action in combating colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of the Anti-Cancer Effects of Free and PLGA-PAA Encapsulated Hydroxytyrosol on the HT-29 Colorectal Cancer Cell Line. Sani, NS., Onsori, H., Akrami, S., et al.[2022]

Hydroxytyrosol significantly increases the expression of the CASP3 gene and the BAX:BCL2 ratio in human colorectal cancer cells, suggesting it may promote apoptosis (cell death) in these cancer cells.

The treatment with hydroxytyrosol also enhances the activity of key antioxidant enzymes and reduces oxidative stress, indicating its potential role in both reducing cancer cell proliferation and improving the antioxidant defense system in colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Hydroxytyrosol on Expression of Apoptotic Genes and Activity of Antioxidant Enzymes in LS180 Cells. Hormozi, M., Salehi Marzijerani, A., Baharvand, P.[2022]

Hydroxytyrosol, a compound found in olive oil, significantly reduces the viability of thyroid cancer cells (papillary and follicular) at high doses by promoting apoptosis and altering key cell cycle regulators like cyclin D1 and p21.

This study is the first to demonstrate that hydroxytyrosol induces cell death in thyroid cancer cells through the intrinsic apoptotic pathway, suggesting its potential as a novel therapeutic target for thyroid cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells. Toteda, G., Lupinacci, S., Vizza, D., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7468519/

Effects of Hydroxytyrosol on Expression of Apoptotic Genes ... Hydroxytyrosol may induce apoptosis in colorectal cancer cells by increasing the expression of CASP3 gene and increasing the BAX:BCL2 ratio.

2. nature.com nature.com/articles/s41598-025-04415-4

Hydroxytyrosol induced ferroptosis through Nrf2 signaling ... Inhibition of cell cycle progression by the hydroxytyrosol-cetuximab combination yields enhanced chemotherapeutic efficacy in colon cancer cells ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1043661822005588

Hydroxytyrosol decreases EDNRA expression through ... Several studies suggest that HT has a protective effect against colorectal cancer (CRC), via different mechanisms [13]. For example, Illesca et al.

4. fjps.springeropen.com fjps.springeropen.com/articles/10.1186/s43094-024-00700-7

Hydroxytyrosol in cancer research: recent and historical ... In an in vitro study on colorectal cancer, hydroxytyrosol inhibited angiogenesis by reducing VEGF expression, suppressing matrix ...

5. spandidos-publications.com spandidos-publications.com/10.3892/etm.2021.10261

Discovery of hydroxytyrosol as thioredoxin reductase 1 ... HT exhibited cellular enzyme inhibitory activity and inhibited proliferation of several colorectal cancer cells (HCT-116, SW620 and HCT-8) at ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10968586/

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention ... In vitro, the effects of low or nutritionally relevant HT doses are poorly explored, and HT is suspected to interfere with colorectal cancer insurgence acting ...

7. withpower.com withpower.com/trial/phase-1-colorectal-neoplasms-11-2024-0da26

Hydroxytyrosol for Colorectal Cancer The toxicological evaluation of hydroxytyrosol suggests a No Observed Adverse Effects Level (NOAEL) of 500 mg/kg/day, indicating a favorable safety profile for ...